The effects of heat waves on the risk of death in the elderly have been well demonstrated, but the total joint burden of climate and multiple pollutants on cardiovascular and cerebrovascular morbidity is not known. Atmospheric pollution may increase the frequency of heat waves and extremes of adverse climatic conditions. We propose an innovative study to integrate our understanding of current and projected climatic conditions with our understanding of pollution exposures, to define "high risk days" when cardiovascular and cerebrovascular health have been most at risk. We will then forecast the magnitude of risk that is related to projected clusters of climatic and pollution conditions over the next 30 years. Preliminary data from our NIH P01 grant (ES09825;Ambient Particles and Cardiac Vulnerability in Humans) suggest that multiple pollutants and adverse climatic conditions jointly increase risk for cardiovascular outcomes. Taking advantage of our P01's precisely collected data on multiple pollutant exposures, and cardiovascular (blood pressure, paroxysmal atrial fibrillation, ventricular tachycardia) and cerebrovascular outcomes (stroke) in Eastern Massachusetts, we will partner with the Atmospheric Chemistry Modeling Group at Harvard: (1) to define "high risk days" for adverse clinical outcomes (e.g., blood pressure changes in people with diabetes;paroxysmal atrial fibrillation/ventricular fibrillation in patients with implantable cardioverter defibrillators;stroke) by clustering days according to climatic conditions and pollution levels;(2) to compare the results of our innovative cluster analyses to more traditional analyses evaluating (a) the associations of short-term exposures to individual weather parameters on the risk of clinical outcomes;(b) effect modification of weather effects by pollutant exposures and sources of vulnerability;and (3) to develop forecasting models to predict changes in blood pressure, and risk of atrial fibrillation, ventricular fibrillation and stroke due to forecasted "high risk days", defined by clustering of adverse climatic conditions and pollution. We will use the Intergovernmental Panel on Climate Change archive of future climate to get expected changes in meteorological variables in 30 years. We will project pollution levels assuming past pollution levels vs change (worsening or improvement) in pollution levels. These projections will be used to estimate changes in the number of "high risk days" between 2000 and 2030, and the subsequent change in the level or number of adverse health outcomes. Once we demonstrate feasibility of our novel approach with our data, it can be applied and evaluated for its relevance in assessment of joint climate and pollution effects in other geographic regions with other health outcomes. Our innovative approach will contribute to public health through defining: (1) the joint pollution and weather conditions that currently are of greatest cardiac and cerebrovascular risk for vulnerable populations;and (2) the health implications for vulnerable populations of projected pollution and climate changes, for an increase (or reduction) in days when they are at high risk for hypertension, hypotension, malignant cardiac arrhythmias and stroke. PUBLIC HEALTH RELEVANCE: Cardiovascular disease and stroke are leading causes of disability and death in the United States and world- wide. We will define and we will forecast "high risk days"---clusters of climatic conditions and air pollution that adversely affect blood pressure, and increase the risk of paroxysmal atrial fibrillation, life-threatening ventricular tachycardia and stroke. Defining and forecasting these "high risk days," given current pollution and climatic conditions and trends, will also help us determine how reduction in pollution or improvement in climatic conditions could improve cardiovascular and cerebrovascular health.